Journal of Thermal Analysis and Calorimetry, Vol.

95 (2009) 3, 891–894

THERMOSTABILITY AND POLYMORPHISM OF THEOBROMA OIL

AND PALM KERNEL OIL AS SUPPOSITORY BASES

M. I. Noordin* and L. Y. Chung

Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

Thermal stability of pharmaceutical ingredients is an important aspect. In this study, we adopted differential scanning calorime-
try (DSC) to investigate thermal stability of suppository bases, theobroma oil (cocoa butter) and a palm kernel oil (PKO) blend. The
study shows theobroma oil possesses six polymorphic forms whilst the palm kernel oil blend has three. Upon rescanning, the PKO
blend does not show changes in the enthalpy of fusion and the melting point with time, whilst the theobroma oil shows significant
reduction, and only regained its thermal stable state after 10 days. This indicates that PKO blend possesses better thermal stability.

Keywords: cocoa butter, DSC, palm kernel oil, pharmaceutical, polymorphism, stability, suppository, theobroma

Introduction mined their suitability as suppository bases using

differential scanning calorimetry (DSC), which is an
The ability of a molecule to crystallize into more than important tool for the study of fat stability [14, 15].
one arrangement is termed polymorphism and it has
profound effect on the shelf life, solubility and formu-
lation [1]. In fat polymorphism, it is the result of dif- Experimental
ferent lateral packing of the fatty acid chains and the
longitudinal stacking of molecules in the lamellae [2]. Materials
Many studies have been conducted to investigate the The hydrogenated palm kernel stearin (Batch
polymorphism profile of various oil and fats products No. 0091420002), palm kernel stearin (Batch
[3–6]. There are three main polymorphic organiza- No. 0091420002) and virgin palm kernel oil (Batch
tions frequently observed in fat, where the arrange- No. 0091420002) were obtained from Cargill (M)
ment of their molecules determine the thermal stabil- Sdn. Bhd., Kuala Lumpur, Malaysia. Theobroma
ity of the fat [7, 8] (Batch No. BD.80.10HF01.0152) was supplied by KL
Polymorphism in a fatty suppository base affects Kepong, Kuala Lumpur, Malaysia. Other chemicals
both the manufacturing process and the quality of the of analytical grade were obtained from either Sigma
finished product, and this has been shown with Chemical Company or Fisher Scientific, U.S.
theobroma as a suppository base [9]. For example, in-
correct storage of theobroma (cocoa butter) based
suppositories at an elevated temperature, such as Preparation of palm kernel oil suppository base
above 30°C, causes the suppositories to melt. Upon The palm kernel oil suppository base was prepared by
cooling, the suppositories harden and metastable mixing hydrogenated palm kernel stearin (50%),
polymorphic forms appear, and this causes the sup- palm kernel stearin (20%) and virgin palm kernel oil
positories to melt at a lower temperature. This prob- (30%) using an Erweka mixer (Model No. AR 402,
lem will be further complicated if the incorporated 45°C, paddle stirrer speed: 100 rpm). The blend was
drug is also prone to polymorphism [10]. allowed to solidify at 25°C for one week and thereaf-
The crystallization kinetics of fats including ter kept at 4°C until use.
theobroma have been studied, however, the time re-
quired for the fats to regain their stable polymorphic DSC analysis
forms after melting has not been widely reported
[7, 8, 11–13]. In this study, we investigated the recov- The differential scanning calorimeter (DSC 6,
ery time of theobroma and a palm kernel oil blend to PerkinElmer, US) was connected to a chiller (C6,
their thermostable polymorphic forms. We also deter- PerkinElmer, US) and a thermal analysis gas station

* Author for correspondence: [email protected]

1388–6150/$20.00 Akadémiai Kiadó, Budapest, Hungary

© 2008 Akadémiai Kiadó, Budapest Springer, Dordrecht, The Netherlands
 NOORDIN, CHUNG

(PerkinElmer, US) to control the flow of the purge by melting of the Form VI polymorph at 36.6°C, which
gas, nitrogen at a flow rate of 20 mL min–1. The DSC gives a dominant peak compared to others (Fig. 1). After
pans used were 50 mL aluminum pans (lids with cooling, the same theobroma sample was subjected to
holes), and indium and zinc (PerkinElmer, US) were immediate remelt, it produced one main peak (Form II)
used to calibrate the DSC. Each sample weighing be- with a melting point of 18°C, and a smaller hump
tween 2.5–4.0 mg (Mettler Toledo UMT2 (Form III) at 26°C. Upon storage, the melting peak in-
Microbalance, Switzerland) was scanned from 3.5 to creased in temperature and only recovered to the origi-
70°C at 5 K min–1 using DSC to give the ‘first melt nal state after storage of 10 days or longer (Table 1 and
DSC curve’. The sample was then cooled from 70 to Fig. 3). This clearly suggests upon melting the crystal
3.5°C at –5 K min–1, followed by storage for 0, structure of the theobroma only regains its original ar-
15 min, 1, 2, 4, 32, 64 h, 5, 10, 20 or 30 days at 22.5°C rangement, thermal stable form after storage at 22.5°C
before rescanned from 3.5 to 70°C at 5 K min–1 to for 10 days. Previously, Davis and Dimick (1989) [11]
give the ‘remelt DSC curve’. The ‘first melt’ and had reported an isothermal study on the crystallization
‘remelt’ scans were determined for each of the three
individual samples at each storage condition for
theobroma oil and palm kernel oil blend.

Results and discussion

The thermal profile of theobroma clearly shows the

presence of 6 polymorphs, which concurs with the work
reported by Loisel et al. (1998) [2], whilst an earlier re-
port suggested the existence of between 4 to 6 poly-
morphs for cocoa butter [15]. The DSC curve shows that
Form I polymorph melts at about 16°C followed by the
crystallization of Form II before it melts at about 21°C.
The Form III polymorph then crystallizes before melting Fig. 1 Comparison of the DSC curves from the a – first melt
at about 26°C followed by the crystallization of and the b – immediate remelt (0 min storage) of
Form IV before it melts at about 29°C Form V then theobroma. Arrows showing the melting peaks of the
crystallizes and melts at about 33°C and this is followed six forms of polymorphs

Table 1 The melting peak, enthalpy change of fusion and % difference of the enthalpy change of fusion compared to the first
melt of theobroma and palm kernel oil blend samples after storage at time intervals at 22.5°C
% difference of enthalpy
Enthalpy change of fusion,
Peak of melting/°C change of fusion, DH
Curves #
Storage time DH/J g–1
relative to the first melt
Theobroma PKO Theobroma PKO Theobroma PKO
a First melt 36.6±0.3 32.6±0.4 111.9±4.3 102.1±2.6 – –
b 0 min 20.1±0.2* 31.3±0.2 55.1±1.0* 98.3±1.7 56.8 3.7
c 15 min 15.5±0.4* 31.7±0.2 44.4±1.4* 98.9±1.9 60.3 3.1
*
d 1h 27.8±0.3 31.7±0.3 62.5±0.8* 100.9±2.0 44.1 1.2
* *
e 2h 27.8±0.4 31.8±0.3 76.5±0.6 101.1±1.3 31.6 1.0
f 4h 27.9±0.4* 31.8±0.3 81.5±0.7* 101.5±1.3 27.2 0.6
* *
g 32 h 32.7±0.3 31.8±0.6 102.0±0.4 101.6±2.0 8.8 0.6
h 64 h 32.8±0.4* 31.9±0.3 102.8±0.5* 101.6±0.6 8.1 0.5
* *
i 5 days 32.9±0.2 31.9±0.6 103.7±0.4 101.7±0.3 7.3 0.4
j 10 days 33.1±0.1* 31.9±0.1 106.0±1.2 101.9±2.0 5.3 0.3
k 20 days 33.4±0.4 32.0±0.5 111.6±1.6 102.4±2.0 0.2 0.3
l 30 days 33.3±0.4 31.1±0.4 111.0±2.8 102.4±2.6 0.8 0.3
#
Representative curves are as depicted in Fig. 3. Each value was expressed as mean (n=3)±SD. PKO: Palm kernel oil blend.
Independent Student’s t-test: * p<0.05 compared to the first melt

892 J. Therm. Anal. Cal., 95, 2009

 THEOBROMA OIL AND PALM KERNEL OIL

characteristics of isolated seed crystals of theobroma at the original Form II polymorph peak. The difference
interval of 0 to 21 h. However, the recovery time to ther- in the melting point of this peak compared to the
mal stable form had not been reported. Form III peak from the first scan is small (1.9±0.2°C)
Tan and Che Man (2000) [16] in their study (Fig. 2). As with theobroma, the palm kernel oil blend
found that there are 4 polymorphic forms for pure was kept at 22.5°C for various time intervals before
PKO, but our study on the PKO blend indicates the being rescanned. However, unlike theobroma, the
existence of 3 polymorphs in the first scanning using enthalpy change of fusion for palm kernel oil blend
DSC. The second scan shows a single peak, close to between the first melt and subsequent remelts were
found to be statistically similar (Fig. 3 and Table 1)
(p>0.05). Similar studies on palm kernel oil have not
been reported, except Siew et al. (2000) [17] had in-
vestigated the thermal characteristics of palm olein
upon short (2 months) and prolong (2 years) storage.
The melting range for theobroma is higher but
narrower (34–39°C) compared to that of palm kernel
oil blend (27–35°C). This suggests unlike complete
melting of palm kernel oil, this theobroma oil may not
afford complete melting in the rectum, as the rectal
temperature is 35–36°C, and this may lead to incom-
plete release of drug.

Conclusions
Fig. 2 Comparison of the DSC curves from the a – first melt
and the b – immediate remelt (0 min storage) of a se- The study supports the use of DSC as a simple method
lected palm kernel oil blend. Arrows showing the melt- to investigate the thermal stability and polymorphism
ing peaks of the three forms of polymorphs of suppository bases. It also indicates palm kernel oil
blend as a superior alternative to theobroma as a sup-
pository base, as it is more thermal stable, and hence,
more robust to temperature change during preparation
and storage.

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DOI: 10.1007/s10973-008-9152-6

894 J. Therm. Anal. Cal., 95, 2009